Abstract
To test the hypothesis that vagal afferent (VA) stimulation modulates the first cervical dorsal horn (C1) neuron activity, which is projected by tooth pulp (TP) afferent inputs through the activation of a local GABAergic mechanism via 5-hydroxytryptamine3 (5-HT3) receptors, we used the technique of microiontophoretic application of drugs. In pentobarbital-anesthetized rats, we recorded C1 spinal neuron activity responding to TP stimulation. The TP stimulation-evoked C1 spinal neuron excitation was inhibited by VA stimulation, and this inhibition was significantly attenuated by iontophoretic application of the 5-HT3 receptor antagonist ICS 205-930 (3-tropanyl-indole-3-carboxylate hydrochloride [endo-8-methyl-8-azabicyclo [3.2.1] oct-3-ol indol-3-yl-carboxylate hydrochloride]) (40 nA) or the GABAA receptor antagonist bicuculline (40 nA). In another series of experiments, we determined that 60 nA iontophoretic application of glutamate produced a maximal increase in the C1 spinal neuron activity at a minimal current. In 53 of 65 neurons (81.5%), VA conditioning stimulation (1.0 mA × 0.1 ms, 50 Hz for 30 s) caused a significant inhibition (35.1%) of the glutamate (60 nA) application-evoked C1 spinal neuron excitation. Iontophoretic application of ICS 205-930 (40 nA) or bicuculline (40 nA) significantly attenuated the VA stimulation-induced inhibition of glutamate iontophoretic application (60 nA)-evoked C1 spinal neuron excitation. These results suggest that VA stimulation-induced suppression of C1 spinal neuron activity, responding to TP stimulation, involve 5-HT3 receptor activation, possibly originating in the descending serotonergic inhibitory system, and postsynaptic modulation of inhibitory GABAergic neurons.
Footnotes
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doi:10.1124/jpet.104.070300.
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ABBREVIATIONS: TP, tooth pulp; spVc, trigeminal spinal nucleus caudalis; C1, the first cervical dorsal horn; NMDA, N-methyl-d-aspartate; VA, vagal afferent; 5-HT, 5-hydroxytryptamine; ICS 205-930, 3-tropanyl-indole-3-carboxylate hydrochloride [endo-8-methyl-8-azabicyclo [3.2.1] oct-3-ol ondol-3-yl-carboxylate hydrochloride]; spVo, trigeminal spinal nucleus oralis; CNS, central nervous system; Imp/s, impulses per second; NRM, nucleus raphe magnus.
- Received April 19, 2004.
- Accepted June 23, 2004.
- The American Society for Pharmacology and Experimental Therapeutics
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